The regulation of histone synthesis during the HeLa cell cycle will be investigated. Measurements of the rate of synthesis of histone mRNA in cells at the beginning of S phase will be carried out. These experiments are directed at distinguishing between several mechanisms for the control of histone synthesis during the S phase. One possibility considered is that histone mRNA synthesis proceeds at all times during the cell cycle, but that histone mRNA is catabolized outside the S phase. Another line of work will examine the stability of histone mRNA in cell extracts obtained from cells blocked in DNA synthesis. In intact cells rapid catabolism of histone mRNA occurs. In the cell extracts this destruction of histone mRNa has not yet been observed. We are trying to understand the mechanism underlying the rapid destruction of histone mRNA upon a block in DNA synthesis. We have found that protein synthesis is necessary for the destruction of histone mRNA. Addition of inhibitors of protein synthesis causes stabilization of the existing mRNA even after DNA synthesis has ceased. However, in vitro protein synthesis in cell free synthesis in cell free systems does not seem to cause the extensive destruction of histone mRNA observed in intact cells.